Journal
ONCOGENE
Volume 22, Issue 52, Pages 8432-8440Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1207180
Keywords
Bcl-x(L); BH4 domain; apoptosis; mitochondria; TAT
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The Bcl-2 family of proteins regulates apoptosis chiefly by controlling mitochondrial membrane permeability. It has previously been shown that the BH4 domain of Bcl-2/Bcl-x(L) is essential for the prevention of apoptotic mitochondrial changes, including the release of cytochrome c and apoptotic cell death. We have previously reported that BH4 peptide fused to the protein transduction domain of HIV-1 TAT protein (TAT-BH4) significantly inhibits etoposide-induced apoptosis in a cell line. This time, we investigated whether TAT-BH4 peptide was cytoprotective in ex vivo and in vivo rodent models. Intraperitoneal injection of TAT-BH4 peptide greatly inhibited X-ray-induced apoptosis in the small intestine of mice and partially suppressed Fas-induced fulminant hepatitis. In addition, this peptide markedly suppressed heart failure after ischemia-reperfusion injury in isolated rat heart, probably by preventing mitochondrial dysfunction. These findings demonstrate that TAT-BH4 peptide exerts antiapoptotic activity both in vivo and ex vivo, and imply that it may be a useful therapeutic agent for diseases involving mitochondrial dysfunction and apoptosis.
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